EU-funded scientists identify key cell in blood-brain barrier
The blood-brain barrier (BBB) plays a crucial role in protecting the brain from harmful substances, yet this powerful shield can be problematic when doctors need to get beneficial drugs into the brain. Now EU-funded researchers in Sweden hint at another component of the BBB which could potentially lead to novel treatment for various diseases. Presented in the journal Nature, the study suggests that pericytes, also known as Rouget cells, are the missing piece to this puzzle. The research was funded in part by the LYMPHANGIOGENOMICS ('Genome-wide discovery and functional analysis of novel genes in lymphangiogenesis'), which received EUR 9 million under the 'Life sciences, genomics and biotechnology for health' Thematic area of the EU's Sixth Framework Programme (FP6). Pericytes are connective tissue cells found in blood capillaries, and in this new study, researchers at the Karolinska Institute in Sweden reveal that they are instrumental to the structure's regulation. 'Our new results show that the blood-brain barrier is regulated by pericytes, and [it] can be opened in a way that allows the passage of molecules of different sizes while keeping the brain's basic functions operating properly,' explains Professor Christer Betsholtz from the institute's Department of Medical Biochemistry, who also led the study. Other organs in the human body are not as impermeable as the BBB; they allow substances to move from the capillaries to the surrounding tissues. In contrast, the BBB blocks this pathway so that certain substances that damage nerve cells, such as plasma proteins, cannot get into the brain. When the BBB is compromised, diseases can arise; over time, researchers have associated capillary permeability in the brain with various disorders including Parkinson's, Alzheimer's and Amyotrophic lateral sclerosis (ALS), commonly referred to as Lou Gehrig's disease. 'Our knowledge of how the BBB is regulated could be used in two ways,' Professor Betsholtz points out. 'To protect the brain under conditions such as stroke and inflammation that lead to the opening of the BBB and the release of neurodamaging substances; and to open the barrier temporarily to allow the transport of drugs against neurodegenerative and other diseases of the brain.' In a nutshell, the pericytes ensure the smooth running of the BBB by an unidentified molecular mechanism. When pericytes are missing, a transport process called transcytosis is kick-started; this opens a path through the capillary walls so that molecules of various sizes, even those nasty plasma proteins, can pass from the blood into the brain. The researchers say pericytes also regulate astrocytes that contribute to the BBB through special extensions, the so-called end-feet, which envelop the capillaries and regulate water and ion flows. 'Another interesting find is that the cancer drug Imatinib, which inhibits certain signal proteins for cell growth, has a similar effect in the presence of pericytes in that they also close the capillary wall transport paths,' Professor Betsholtz says. Researchers from the Sahlgrenska Academy in Sweden contributed to this study.
Countries
Sweden